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Biomedical subjects

C L White

Publications and source records attributed to C L White.

At least 109 records · Page 6Linked to original sources

Effect of zinc depletion on angiotensin I-converting enzyme in arterial walls and plasma of the rat.

The effect of zinc depletion and of additional angiotensin I-converting enzyme (ACE) inhibitor treatment was studied on ACE in aortic and other tissues, in plasma and on systolic blood pressure of the rat. Zinc deprivation significantly reduced plasma zinc concentration, plasma and testicular ACE activities and blood pressure, but stimulated aortic ACE while lung values remained constant. Zinc deficiency combined with ACE inhibition further suppressed plasma ACE and stimulated the aortic enzyme earlier. Zinc repletion experiments (in vitro) suggest the existence of a feedback mechanism controlling ACE synthesis depending on plasma ACE activity.

Angiotensin-Converting Enzyme Inhibitors↗

Suprasellar germ cell tumors in the dog: a report of five cases and review of the literature.

Suprasellar germ cell tumors were identified in five young adult to middle-aged dogs. Clinical signs included depression, mydriasis, ptosis and visual deficit. At necropsy large extramedullary masses were found on the ventral surface of the rostral brain stem. Histologically four were characterized by sheets and nests of moderately pleomorphic round cells resembling seminoma, admixed with larger vacuolated cells, glandular formations with secretory material, and occasional foci of squamous differentiation. The fifth case was more homogeneous, with germinomatous elements predominating. Immunohistochemical examination of three tumors revealed positive staining for alpha fetoprotein. Although only one case showed intracranial metastasis, these tumors were considered malignant due to the marked local invasion and destruction. The veterinary literature is reviewed, and we propose that two tumors previously reported as craniopharyngioma be reclassified as germ cell tumors. One other tumor previously reported as an unclassified suprasellar tumor was identified, which also demonstrated features of a germ cell tumor.

Animals↗

Relationship between plasma zinc, angiotensin-converting enzyme, alkaline phosphatase and onset of symptoms of zinc deficiency in the rat.

Recent evidence suggests that changes in plasma zinc concentration may play a central role in the development of early lesions of zinc deficiency. The aim of the following work was to better understand events occurring in plasma during the onset of zinc deficiency, and to investigate biochemical mechanisms by which plasma zinc may exert its effects. Fifty male weanling rats of 90 g weight were allocated to five treatment groups of ten rats each. Treatments were: 1, zinc deficient, mixed diet (1-2 mg Zn per kg): 2, zinc deficient, self-select diet; 3, zinc repleted; 4, control, pair fed; 5, control, ad libitum fed. With the exception of treatment 1, which consisted of a 25% casein diet, all rats were offered protein as a separate component of the diet. Control rats received zinc in the drinking water (100 mg l-1). The sequence of events following initiation of zinc deficiency were: reduced plasma zinc concentration (2 days), reduced plasma angiotensin-converting enzyme and alkaline phosphatase activities (3-4 days), reduced feed intake and growth (5-6 days) and reduced percentage protein intake (12 days). Plasma zinc concentration in the deficient rats was inversely correlated with the growth rate of the rat over the previous 24 h. Zinc repletion resulted in marked overshoot in plasma zinc concentration (300%) and converting-enzyme activity (150%) within 24 h, but a return to normal within 72 h. Alkaline phosphatase activity responded likewise, albeit more slowly. Protein self selection had no effect on the manifestations of zinc deficiency, although reduced protein intake was associated with lower plasma zinc concentration. The results provide evidence of a role for plasma zinc in the development of early clinical signs of zinc deficiency, possibly acting biochemically through reduced activity of zinc-dependent peptidases such as angiotensin-converting enzyme.

Alkaline Phosphatase↗

The effects of ammonium tetrathiomolybdate intake on tissue copper and molybdenum in pregnant ewes and lambs.

Pregnant ewes (d 32 of gestation) were allocated to three treatments and given intraruminal controlled-release devices designed to deliver 0, 20 or 60 mg diammonium tetrathiomolybdate (TTM) per day. Ewes given 20 or 60 mg TTM/d also received an oral drench of 120 or 360 mg TTM twice weekly commencing on d 86 of gestation. Liver and kidney samples were taken from lambs 48 h after birth and from ewes on d 18 postpartum. Trichloroacetic acid soluble Cu, ceruloplasmin and superoxide dismutase activities in the plasma of ewes were decreased (P less than .05) by TTM. Liver Cu concentrations were decreased (P less than .05), but kidney Cu concentrations increased (P less than .05) by 16-fold in ewes given the higher dose of TTM. Liver and kidney Mo concentrations were elevated (P less than .05) 9- and 30-fold, respectively, in ewes given TTM. Plasma glucose concentrations in ewes were decreased (P less than .05) by the highest level of TTM treatment. Lambs of ewes given TTM had a fivefold increase (P less than .05) in liver Mo concentration, but kidney Mo concentration was not affected (P greater than .05) and liver Cu concentration was reduced (P less than .05). In ewes, Mo apparently caused Cu to be mobilized from the liver and a Cu and Mo complex accumulated in the kidney. Some Mo crossed the placenta, but only limited Mo accumulated in the fetal livers. When given to pregnant ewes, TTM reduced liver Cu levels in the lambs but did not affect the concentration of Cu in colostrum.

Animals↗

Isolation of the insoluble straight fibrils of Pick's disease.

This paper describes the isolation and partial purification of the straight fibrils that occur in the neurons of Pick's disease. Pick fibrils are highly insoluble in a variety of solvents. These fibrils were shown to be sodium dodecyl sulfate insoluble even in the presence of a reducing agent at elevated temperatures. This allowed the selective isolation of the fibrils using the SDS boiling procedure and sucrose gradient centrifugation that have been described for isolation of paired helical filaments of Alzheimer's disease. The isolated fibrils retained the native morphology seen in tissue sections, but some appeared to become unraveled to yield a paired helical appearance. These results indicate that the Pick fibrils have many chemical and structural characteristics in common with Alzheimer paired helical filaments, and suggest that these two diseases may be closely related.

Aged↗

Alzheimer's disease: neurofibrillary tangles in nuclei that project to the cerebral cortex.

We have used an antibody to the paired helical filament protein to immunohistochemically identify the regional distribution of subcortical nuclei containing neurofibrillary tangles in brains from Alzheimer's disease patients. Sections were examined from the cerebral cortex, diencephalon, midbrain and pons in seven Alzheimer's and three age-matched normal brains. The antibody sensitively stained the many tangles, and senile plaques, in the cerebral cortex of the Alzheimer's brains and the few tangles and senile plaques in the aged normal cortex. Ten subcortical nuclei contained many tangles in the Alzheimer's brains. The tangles were found not only within the locus coeruleus and dorsal raphe nucleus, which often have been shown to be involved in Alzheimer's neuropathology, but also within several other nuclei not previously related to this disease. For example, tangles were found in the nucleus paranigralis, peripeduncular nucleus, medial parabrachial nucleus and several midline thalamic nuclei. All of the nuclei which contained tangles have been shown, in neuroanatomical tracing studies, to project to the cerebral cortex. These data indicate that Alzheimer's disease is a disease of the cerebral cortex and the numerous subcortical nuclei which diffusely innervate it, and are consistent with the hypothesis that the cerebral cortex is the primary target of the disease and the interconnected subcortical nuclei are secondarily affected due to retrograde transport of a cortical pathogen or failure of normal transport of a trophic agent.

Afferent Pathways↗

Comparison of dark-field microscopy and a flagella stain for monitoring the effect of a Water Pik on bacterial motility.

The purpose of this examiner-blind study was threefold: to compare the microbial counts obtained by two different techniques for assessing bacterial motility, to assess the inter-rater reliability of these two techniques and to evaluate the effect of a water irrigating device (Water Pik) on bacterial motility at 3- and 6-mm probing depths. Subgingival plaque samples were taken from 10 healthy patients having at least two sites that probed greater than 6 mm, (one control, one experimental). Half of the patients were sampled at 3 mm, the other half at 6 mm, both at baseline (Day 0) and at Day 21. Two slides were prepared from each plaque sample, one for dark-field evaluation and one stained with a simplified silver-plating technique for flagella. All slides were read simultaneously by 3 observers, and the per cent motility calculated for spirochetes, motiles and all others. Strong positive inter-rater reliability correlations ranging from r = 0.95 to r = 0.99 were found for both the dark-field and flagella staining techniques. Spirochete counts obtained by both techniques were highly correlated (r = 0.91), whereas counts for motiles resulted in negative correlations between the techniques. Dark-field counts were consistently higher than the flagella stain counts for motile rods. Spirochetes were reduced, but not significantly, after irrigation of both 3-mm and 6-mm sites. Bacterial motility can be evaluated by both dark-field and flagella-staining techniques with a high degree of inter-rater reliability.

Adult↗

The effect of zinc in vivo and in vitro on the activities of angiotensin converting enzyme and kininase-I in the plasma of rats.

Two groups of rats were pair fed, for 18 days, diets containing either 2.6 (Zn deficient) or 100 mg Zn/kg (control diet). Plasma was assayed spectrophotometrically for the activity of kininase-I and angiotensin converting enzyme (ACE) in the presence of varying concentrations of added Zn2+. Zinc deficient rats had only 76% of the activity of both kininase-I and ACE compared with zinc supplemented control rats. There was a significant linear relationship between enzyme activity and concentration of zinc in plasma for both enzymes. When zinc was added to the enzyme incubation mixture for zinc deficient rats, the activity of ACE increased by 73% and that of kininase-I by 33%. This Zn2+-stimulated increase in enzyme activity was negatively correlated with the in vivo concentration of zinc in plasma, and a plateau in enzyme activity was seen at concentrations of plasma zinc that were commensurate with normal zinc status (over 14 mumol/1). The results demonstrate that the activities of both kininase-I and ACE are dependent on the concentration of zinc in vivo and in vitro, and suggest that information concerning the concentration of zinc in plasma and assay solutions be a prerequisite solutions be a prerequisite for the use of these enzymes in the clinical diagnosis of disease states. The results also showed that the activity of ACE and kininase-I in plasma could be used for the biochemical diagnosis of a suboptimal zinc status.

Angiotensin-Converting Enzyme Inhibitors↗

Primary degenerative dementia without Alzheimer pathology.

To define the pathology in cases of non-Alzheimer primary degenerative dementia (non-AD PDD), we have studied autopsies from four medical centres accessioned in consecutive years since 1976. Neurochemical studies of the basal forebrain-cortical (BF-C) cholinergic system have been conducted in cases from which frozen tissue was available. Twenty-two cases (mean age 70 years, range 47-86) in which the history was consistent with PDD, but which did not meet anatomic criteria for AD, were selected. Approximately 70 cases of PDD, which were accessioned in the same years and met the anatomic criteria for AD, were excluded. The pathologic findings permitted a classification into six groups: Lewy body disease (LBD), 4 cases; Pick's disease, 6 cases: cortical degeneration with motor neuron disease (CDmnd), 2 cases; hippocampal and temporal lobe sclerosis, 3 cases; few or nonspecific abnormalities, 5 cases; other disorders, 2 cases. Our findings suggest that LBD and Pick's disease account for a large proportion of cases of non-AD PDD in the presenile age group, but that a large number of other disorders occasionally present as PDD. Careful examination of the motor systems, as well as cerebral structures relate to cognitive function, is important in the neuropathologic evaluation. Lesions of the BF-C cholinergic system have been most consistent and severe in LBD, and have not been identified in CDmnd.

Aged↗

Cortical degeneration with swollen chromatolytic neurons: its relationship to Pick's disease.

We report two cases of dementia in which cortical degeneration with widespread swollen chromatolytic neurons (SCN) was the dominant pathologic feature. Each patient had received the diagnosis of Alzheimer's disease on the basis of clinical findings. There was no deficit of cortical choline acetyltransferase activity, assayed in one case, or lesions of the nucleus basalis of Meynert. The brains had moderate to marked frontal atrophy. Comparison of SCN with several other cerebral degenerative disorders indicates a similarity with certain features of the transmissible spongiform encephalopathies and with corticodentatonigral degeneration. The pathologic features of our cases are those of a number of other cases reported as "Pick's disease," and may represent an earlier stage in the pathogenetic process than the severe, sharply circumscribed atrophy with "nonspecific" cell loss and gliosis as the only microscopic residuals. Our findings re-emphasize the need to search for pathogenetically distinct subgroups which have been wholly or partially subsumed into the concept of Pick's disease.

Acetylcholine↗

Nonbacterial thrombotic endocarditis in bone marrow transplant patients.

We reviewed the findings in 2381 consecutive autopsies, a series containing 91 bone marrow transplant (BMT) patients, and found 45 cases of nonbacterial thrombotic endocarditis (NBTE). The overall prevalence of NBTE was 1.9%. NBTE was present in seven BMT patients, for a prevalence of 7.7%. The rate of NBTE in BMT patients was significantly greater than the rate of NBTE in the general autopsy population (P less than 0.001). The frequency of NBTE was not increased in patients with the individual underlying diseases for which BMT was a possible treatment (the BMT candidate diseases [BMTCD]). When rates of NBTE were compared in patients with BMTCD, there was a significantly higher rate in patients who had received BMT than in those who had not (P less than 0.02). These findings indicate that NBTE occurs with greater frequency in BMT patients and that there may be features of the BMT regimen that predispose patients to develop NBTE. Although several factors related to BMT are discussed as potential contributors to the increased prevalence of NBTE, we were not able to demonstrate an association between NBTE and any single factor. Since NBTE is an important cause of arterial embolization, an awareness of the increased frequency of NBTE in BMT patients is important for clinicians who must interpret neurologic and other abnormalities in BMT recipients.

Adolescent↗

Neurologic complications of bone marrow transplantation.

Among 78 patients who died after bone marrow transplantation, neurologic complications were present in 55 (70%) and were the cause of death in 5 (6%). Metabolic encephalopathy occurred in 29 patients (37%). CNS infections included aspergillosis (3), herpes simplex encephalitis (2), and Listeria monocytogenes meningitis (1). Six additional patients had neuropathologic changes possibly due to cytomegalovirus infection. Cerebrovascular complications occurred in five patients (two hemorrhages and three infarcts). All infarcts were associated with endocarditis. The rate of nonbacterial thrombotic endocarditis was significantly higher (p less than 0.001) than in the general autopsy population. CNS leukemia and therapy-induced injury were rare. There was no evidence of graft-versus-host disease involving the CNS.

Adolescent↗